The principal objective of the proposed study is to evaluate the role of DNA repair during the initiation of hepatocarcinogenesis. Two systems, namely rat liver in vivo and rat hepatocytes in primary monolayer culture, will be employed. The greatest effort will be devoted to the latter cell system. Studies will be conducted to quantify the DNA repair capacity of the cultured hepatocytes using detection of both unscheduled DNA synthesis and repair replication. Next, a comparison of DNA repair following treatment of these cells with various hepatocarcinogens of differing carcinogenicity will be done. The results will be compared to those obtained from the in vivo studies. In addition, the DNA repair capacity of the cultured hepatocytes will be compared quantitatively with that of hepatoma cells and other rat cells in primary culture. These studies will yield new information concerning the value of the primary rat hepatocyte culture system for possible use in studies concerning screening chemicals for potential carcinogenicity as well as studies in the mechanisms of carcinogenesis.